This trial will study if it is beneficial in terms of blood sugar control, and safe, to add liraglutide to anti-diabetes medication like sodium-glucose co- transporter 2 (SGLT2) inhibitor with or without metformin.

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/07/008990
• Date of registration: 06-07-2017
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk India Private Ltd
• Public title: This trial will study if it is beneficial in terms of blood sugar control, and safe, to add liraglutide to anti-diabetes medication like sodium-glucose co- transporter 2 (SGLT2) inhibitor with or without metformin.
• Scientific title: "This is a 26-week, confirmatory, randomised, double-blind, placebo-controlled, multicentre, multinational, two-arm, parallel-group trial, investigating the effect and safety of adding liraglutide 1.8 mg/day to pre-trial treatment with any SGLT2 inhibitor (as monotherapy or in combination withmetformin) in subjects with T2DM who have not achieved adequate glycaemic control despite stable treatment with SGLT2 inhibitor ± metformin for at least 90 days prior to trial participation. "
• Date of first enrolment: 19-07-2017
• Target sample size: 303
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=17708
• Study type: Interventional
• Study design: Randomized, Parallel Group, Placebo Controlled Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Double Blind Double Dummy
• Phase: Phase 3

Countries of recruitment

Argentina, Brazil, Canada, India, Ireland, Italy, Lebanon, Malaysia, Mexico, Sweden, United Kingdom, United States of America

Contacts

• Name: Dr Anil N Shinde
• Affiliation: Novo Nordisk India Private Ltd.

• Name: Dr Anil N Shinde
• Affiliation: Novo Nordisk India Private Ltd.

Key inclusion & exclusion criteria

Inclusion criteria: 1. Informed consent obtained before any trial-related activities. Trial-related activities are any

procedures that are carried out as part of the trial, including activities to determine suitability

for the trial.

2. Male or female, age >= 18 years at the time of signing informed consent.

3. Diagnosed with type 2 diabetes mellitus.

4. HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive).

5. Stable dose of an SGLT-2 inhibitor as monotherapy or in combination (including fixed-dose

drug combination) with a stable dose of metformin (>= 1500 mg or maximum tolerated dose)

for at least 90 days prior to the day of screening. All medications in compliance with current

local label.

6. Body mass index greater than 20 kg/m2."


Exclusion criteria: 1. Known or suspected hypersensitivity to trial product(s) or related products.

2. Previous participation in this trial. Participation is defined as signed informed consent.

3. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing

potential and not using an adequate contraceptive method (adequate contraceptive measure

as required by local regulation or practice).Brazil: According to resolution 466/12: Regarding exclusion criterion: Female who is

pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not

using adequate contraceptive methods (adequate contraceptive measures as required by local

regulation or practice). For women who expressly declare free of the risk of pregnancy, either

by not engaging in sexual activity or by having sexual activity with no birth potential risk, use of

contraceptive method will not be mandatory.

4. Receipt of any investigational medicinal product within 90 days before screening.

5. Treatment with any medication for the indication of diabetes or obesity other than stated in

the inclusion criteria within the past 90 days prior to the day of screening. However, short

term insulin treatment for a maximum of 14 days during the 90 days prior to the day of

screening is allowed.

6. Any disorder which in the investigatorâ??s opinion might jeopardise subjectâ??s safety or

compliance with the protocol.

7. History of diabetic ketoacidosis while being treated with SGLT2 inhibitors.

8. Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid

carcinoma. Family is defined as a first degree relative.

9. History or presence of pancreatitis (acute or chronic).

10. Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of < 60

mL/min/1.73m2 as defined by KDIGO1 classification using isotope dilution mass

spectrometry (IDMS) for serum creatinine measured at screening.

11. Impaired liver function, defined as ALT >=2.5 times upper normal limit at screening.

12. Subjects presently classified as being in New York Heart Association (NYHA) Class IV.

13. Planned coronary, carotid or peripheral artery revascularisation known on the day of

screening.

14. Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or

transient ischaemic attack within the past 180 days prior to the day of screening.

15. Inadequately treated blood pressure defined as Grade 3 hypertension or higher (systolic

>=180 mmHg or diastolic >=110 mmHg) at screening.



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Type 2 Diabetes

Intervention(s)

Intervention1: Liraglutide
: Liraglutide will be initiated with a starting dose of 0.6 mg/day, with subsequent weekly
dose escalations of 0.6 mg/day in accordance with the approved dose escalation for liraglutide until
the maintenance dose of 1.8 mg/day in this trial is reached. Escalation from 0.6 to 1.2 then 1.8
mg/day can be extended by 7 days in total if subjects do not tolerate an increase in dose during dose
escalation, at the discretion of the investigator.
duration : 29 weeks
route of administration: subcutaneous
Control Intervention1: Placebo:
Placebo will be initiated with a starting dose of 0.6 mg/day, with subsequent weekly
dose escalations of 0.6 mg/day in accordance with the approved dose escalation for liraglutide until
the maintenance dose of 1.8 mg/day in this trial is reached. Escalation from 0.6 to 1.2 then 1.8
mg/day can be extended by 7 days in total if subjects do not tolerate an increase in dose during dose
escalation, at the discretion of the investigator.
duration : 29 weeks
route of administration: subcutaneous

Primary Outcome(s)

To compare the effect of liraglutide 1.8 mg/day versus placebo as add-on to an SGLT2 inhibitor ± metformin on glycaemic control in subjects with type 2 diabetes mellitus.

Timepoint: Change from baseline to week 26

Secondary Outcome(s)

To compare the effect of liraglutide 1.8 mg/day versus placebo as add-on to an SGLT2 inhibitor ±

metformin in subjects with type 2 diabetes mellitus with regards to:

Body weight related parameters

Selected cardiovascular risk factors

SafetyTimepoint: Change from baseline to week 26 in body weight

To compare the effect of liraglutide 1.8 mg/day versus placebo as add-on to an SGLT2 inhibitor ±

metformin in subjects with type 2 diabetes mellitus with regards to:

selected glucose metabolism parametersTimepoint: Change from baseline to week 26 in body weight

Secondary ID(s)

NN2211-4315 version 2.0 dated 26 Oct 2016

U1111-1184-8086

Source(s) of Monetary Support

Novo Nordisk India Private Ltd. "Plot No.32, 47 - 50, EPIP Area, Whitefield" Bangalore Karnataka 560 066

Ethics review

Status: Approved
Approval date: 19/12/2016
Contact:

Ethics Committee of Diabetes Thyroid Hormone Research Institute

Status: Approved
Approval date: 30/01/2017
Contact:

Institutional Ethics Committee of Kovai Diabetes Specialty Centre and Hospital

Status: Approved
Approval date: 02/02/2017
Contact:

Human Welfare Ethical Committee for Human Sciences and Research

Status: Approved
Approval date: 06/02/2017
Contact:

ILS Hospital Ethics Committee

Status: Approved
Approval date: 03/03/2017
Contact:

Ethics Committee of Manipal Hospitals

Status: Approved
Approval date: 25/04/2017
Contact:

AMC MET Ethics Committee

Status: Approved
Approval date: 12/06/2017
Contact:

Ethics Committee for Human Research Lady Hardinge Medical College and S.S.K. Hospital

Status: Approved
Approval date: 31/07/2017
Contact:

Institutional Ethics Committee(IEC) Department of Research 6th Floor C Wing Deenanath Mangeshkar Hospital and Research Centre

Status: Approved
Approval date: 08/08/2017
Contact:

Institutional Ethics Committee Gandhi Medical College and Hospital

Results

• Date Completed: 08/05/2018